Glucose-induced insulin secretion and net calcium uptake were simultaneously studied in isolated islets obtained from normal, adrenalectomized, ovariectomized and radiothyroidectomized rats, as well as from the corresponding hormone deprived rats following the administration of specific substitutive therapy. Both parameters were also studied in islets from normal rats incubated in the presence of Trifluoperazine (TFP). In all these unrelated experimental conditions simultaneous changes were obtained, observed in the release of insulin and the net calcium uptake elicited by glucose. Otherwise, the modifications of these two parameters obtained in the hormone deprived states were brought back to normal when the animals received the specific substitutive hormonal treatment. On the other hand, TFP also induces simultaneous diminution in both glucose-induced insulin release and net calcium uptake by isolated islets. On account of our results, we could suggest that the mechanism involved in the control of the glucose-induced net calcium uptake is actively modulated by adrenal and ovarian steroids and thyroid hormones as well as by calmodulin. Therefore, changes induced either in the level or activity of these modulators will modify the rate of influx and efflux of Ca2+ across the plasma membrane, with the consequent alteration in the mechanism of stimulus: secretion coupling of insulin.